Targeted Oncology

, Volume 8, Issue 2, pp 117–125 | Cite as

Cytokines associated with toxicity in the treatment of recurrent glioblastoma with aflibercept

  • Nicole Shonka
  • Yuji Piao
  • Mark Gilbert
  • Alfred Yung
  • Susan Chang
  • Lisa M. DeAngelis
  • Andrew B. Lassman
  • Jun Liu
  • Timothy Cloughesy
  • H. Ian Robins
  • Rita Lloyd
  • Alice Chen
  • Michael Prados
  • Patrick Y. Wen
  • John Heymach
  • John de Groot
Original Research

Abstract

Plasma profiling of patients treated with antiangiogenic agents may identify markers that correlate with toxicity. Objectives were to correlate changes in cytokine and angiogenic factors as potential markers of toxicity to aflibercept. Circulating cytokine and angiogenic factors were measured in 28 patients with recurrent glioblastoma in a single-arm phase II study of aflibercept. Plasma samples were analyzed at baseline, 24 h, and 28 days using multiplex assays or ELISA. We evaluated log-transformed baseline biomarker expressions with Cox proportional hazard regression models to assess the effect of markers on any grade II–IV (Gr II–IV) toxicity, on-target toxicity (hypertension, proteinuria, thromboembolism), and fatigue. All tests were two sided with a statistical significance level of p = 0.05. Among 28 pts, there were 116 Gr II–IV events. Changes in IL-13 from baseline to 24 h predicted on-target toxicities. Increases in IL-1b, IL-6, and IL-10 at 24 h were significantly associated with fatigue. Progression-free survival was 14.9 months for patients in the all-toxicity group and 9.0 months for patients in the on-target toxicity group compared to 4.3 months for those who did not develop any Gr II–IV toxicity (p = 0.002 and p = 0.045, respectively). Toxicity from antiangiogenic therapy remains an important cause of antiangiogenic treatment discontinuation and patient morbidity. Changes in IL6, IL10, and IL13 were repeatedly correlated with toxicity. Profiling of IL-13 as a surrogate for endothelial dysfunction could individualize patients at risk during antiangiogenic therapy, as could identifying those at higher risk for fatigue using IL-6 and IL-10.

Keywords

Glioblastoma Aflibercept VEGF Cytokines Toxicity 

Notes

Funding

Funding was received from the National Institutes of Health [U01-CA62399 to NABTC, 1R21A126127 to J. de G.] and the ASCO Career Development Award [to J. de G.].

Conflict of interest

We report that no funds or benefits of any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Supplementary material

11523_2013_254_MOESM1_ESM.pdf (38 kb)
ESM 1(PDF 38 kb)
11523_2013_254_MOESM2_ESM.pptx (368 kb)
Supplemental Figure 1Skin biopsy with Hematoxylin and Eosin (H&E) staining at 4× (A) and 20× (B) magnification. Histology showed psoriasiform epidermal hyperplasia with pallor of the upper epidermis, reminiscent of acrodermatitis enteropathica or other deficiency dermatosis. (PPTX 367 kb)

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Copyright information

© Springer-Verlag France 2013

Authors and Affiliations

  • Nicole Shonka
    • 1
  • Yuji Piao
    • 2
  • Mark Gilbert
    • 2
  • Alfred Yung
    • 2
  • Susan Chang
    • 3
  • Lisa M. DeAngelis
    • 4
  • Andrew B. Lassman
    • 5
  • Jun Liu
    • 2
  • Timothy Cloughesy
    • 6
  • H. Ian Robins
    • 7
  • Rita Lloyd
    • 7
  • Alice Chen
    • 8
  • Michael Prados
    • 3
  • Patrick Y. Wen
    • 9
  • John Heymach
    • 2
  • John de Groot
    • 2
  1. 1.Division of Oncology and HematologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.M.D. Anderson Cancer CenterUniversity of TexasHoustonUSA
  3. 3.University of California San FranciscoSan FranciscoUSA
  4. 4.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  5. 5.Department of Neurology and Herbert Irving Comprehensive Cancer CenterNew York-Presbyterian/Columbia University Medical CenterNew YorkUSA
  6. 6.University of California Los AngelesLos AngelesUSA
  7. 7.University of Wisconsin Medical SchoolMadisonUSA
  8. 8.NIH, NCI and CTEPBethesdaUSA
  9. 9.Dana Farber Cancer InstituteBostonUSA

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